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FEMS Microbiology Letters Jan 2024Pseudomonas aeruginosa is an opportunistic pathogen that recently has been increasingly isolated from foods, especially from minimally processed fish-based products....
Global transcriptome analysis of Pseudomonas aeruginosa NT06 response to potassium chloride, sodium lactate, sodium citrate, and microaerophilic conditions in a fish ecosystem.
Pseudomonas aeruginosa is an opportunistic pathogen that recently has been increasingly isolated from foods, especially from minimally processed fish-based products. Those are preserved by the addition of sodium chloride (NaCl) and packaging in a modified atmosphere. However, the current trends of minimizing NaCl content may result in an increased occurrence of P. aeruginosa. NaCl can be replaced with potassium chloride (KCl) or sodium salts of organic acids. Herein, we examined the antimicrobial effects of KCl, sodium lactate (NaL), sodium citrate (NaC), and sodium acetate (NaA) against P. aeruginosa NT06 isolated from fish. Transcriptome response of cells grown in medium imitating a fish product supplemented with KCl and KCl/NaL/NaC and maintained under microaerophilic conditions was analysed. Flow cytometry analysis showed that treatment with KCl and KCl/NaL/NaC resulted in changed metabolic activity of cells. In response to KCl and KCl/NaL/NaC treatment, genes related to cell maintenance, stress response, quorum sensing, virulence, efflux pump, and metabolism were differentially expressed. Collectively, our results provide an improved understanding of the response of P. aeruginosa to NaCl alternative compounds that can be implemented in fish-based products and encourage further exploration of the development of effective methods to protect foods against the P. aeruginosa, underestimate foodborne bacteria.
Topics: Pseudomonas aeruginosa; Potassium Chloride; Animals; Sodium Citrate; Sodium Lactate; Gene Expression Profiling; Fishes; Citrates; Anti-Bacterial Agents; Sodium Acetate; Transcriptome; Ecosystem; Food Microbiology
PubMed: 38845372
DOI: 10.1093/femsle/fnae043 -
Forensic Science, Medicine, and... Jun 2024Complex suicides are rare occurrences that can be categorized into planned (or primary) cases and unplanned (or secondary) cases. Additionally, individuals often select...
Complex suicides are rare occurrences that can be categorized into planned (or primary) cases and unplanned (or secondary) cases. Additionally, individuals often select suicide methods based on their availability and accessibility. The body of a 58-year-old man was discovered deceased inside his medical office. He was found seated on the waiting room sofa, with his airways obstructed by several layers of adhesive tape wrapped around his head. An intravenous needle was observed in his left arm, and on the table in front of him, an empty 50 ml syringe, two empty vials of 10 ml potassium chloride, and an empty 10 mg vial of Valium (diazepam) were found. A roll of adhesive tape, similar to the one around his head, was also present. The autopsy, conducted 36 h after the body's discovery, revealed therapeutic concentrations of diazepam and its metabolite nordiazepam in the blood samples, while potassium chloride was not detected. Integrating forensic findings obtained from autopsy, histology, and other postmortem investigation, including toxicological analysis, can aid in defining suicidal behavior and preventing misinterpretation, particularly in differentiating diagnosis between homicide and suicide. It is crucial to consider circumstantial data and professional knowledge in such cases.
PubMed: 38839741
DOI: 10.1007/s12024-024-00836-1 -
The Journal of Biological Chemistry Jun 2024Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters....
Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters. Ablation of ClC‑K/barttin chloride channels causes deafness by interfering with the positive electrical potential of the endolymph, but roles of other anion channels in the inner ear have not been studied. Here we report the intracochlear distribution of all five LRRC8 subunits of VRAC, a volume-regulated anion channel that transports chloride, metabolites, and drugs such as the ototoxic anti-cancer drug cisplatin, and explore its physiological role by ablating its subunits. Sensory hair cells express all LRRC8 isoforms, whereas only LRRC8A, D and E were found in the potassium-secreting epithelium of the stria vascularis. Cochlear disruption of the essential LRRC8A subunit, or combined ablation of LRRC8D and E, resulted in cochlear degeneration and congenital deafness of Lrrc8a mice. It was associated with a progressive degeneration of the organ of Corti and its innervating spiral ganglion. Like disruption of ClC-K/barttin, loss of VRAC severely reduced the endocochlear potential. However, the mechanism underlying this reduction seems different. Disruption of VRAC, but not ClC-K/barttin, led to an almost complete loss of Kir4.1 (KCNJ10), a strial K channel crucial for the generation of the endocochlear potential. The strong downregulation of Kir4.1 might be secondary to a loss of VRAC-mediated transport of metabolites regulating inner ear redox potential such as glutathione. Our study extends the knowledge of the role of cochlear ion transport in hearing and ototoxicity.
PubMed: 38838775
DOI: 10.1016/j.jbc.2024.107436 -
The Journal of Chemical Physics Jun 2024Thermophoresis, or thermodiffusion, is becoming a more popular method for investigating the interactions between proteins and ligands due to its high sensitivity to the...
Thermophoresis, or thermodiffusion, is becoming a more popular method for investigating the interactions between proteins and ligands due to its high sensitivity to the interactions between solutes and water. Despite its growing use, the intricate mechanisms behind thermodiffusion remain unclear. This gap in knowledge stems from the complexities of thermodiffusion in solvents that have specific interactions as well as the intricate nature of systems that include many components with both non-ionic and ionic groups. To deepen our understanding, we reduce complexity by conducting systematic studies on aqueous salt solutions. In this work, we focused on how guanidinium salt solutions behave in a temperature gradient, using thermal diffusion forced Rayleigh scattering experiments at temperatures ranging from 15 to 35 °C. We looked at the thermodiffusive behavior of four guanidinium salts (thiocyanate, iodide, chloride, and carbonate) in solutions with concentrations ranging from 1 to 3 mol/kg. The guanidinium cation is disk-shaped and is characterized by flat hydrophobic surfaces and three amine groups, which enable directional hydrogen bonding along the edges. We compare our results to the behavior of salts with spherical cations, such as sodium, potassium, and lithium. Our discussions are framed around how different salts are solvated, specifically in the context of the Hofmeister series, which ranks ions based on their effects on the solvation of proteins.
PubMed: 38828819
DOI: 10.1063/5.0215843 -
Physiologia Plantarum 2024Halophyte Halogeton glomeratus mostly grows in saline desert areas in arid and semi-arid regions and is able to adapt to adverse conditions such as salinity and drought....
Halophyte Halogeton glomeratus mostly grows in saline desert areas in arid and semi-arid regions and is able to adapt to adverse conditions such as salinity and drought. Earlier transcriptomic studies revealed activation of the HgS2 gene in the leaf of H. glomeratus seedlings when exposed to saline conditions. To identify the properties of HgS2 in H. glomeratus, we used yeast transformation and overexpression in Arabidopsis. Yeast cells genetically transformed with HgS2 exhibited K uptake and Na efflux compared with control (empty vector). Stable overexpression of HgS2 in Arabidopsis improved its resistance to salt stress and led to a notable rise in seed germination in salinity conditions compared to the wild type (WT). Transgenic Arabidopsis regulated ion homeostasis in plant cells by increasing Na absorption and decreasing K efflux in leaves, while reducing Na absorption and K efflux in roots. In addition, overexpression of HgS2 altered transcription levels of stress response genes and regulated different metabolic pathways in roots and leaves of Arabidopsis. These results offer new insights into the role of HgS2 in plants' salt tolerance.
Topics: Arabidopsis; Plants, Genetically Modified; Salt Tolerance; Salt-Tolerant Plants; Gene Expression Regulation, Plant; Sodium; Plant Proteins; Potassium; Plant Leaves; Plant Roots; Sodium Chloride; Germination; Amaranthaceae
PubMed: 38828569
DOI: 10.1111/ppl.14356 -
Drug Design, Development and Therapy 2024Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed...
PURPOSE
Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.
METHODS
This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.
RESULTS
The 90% CI of the ratio of geometric means (combination: monotherapy) for AUC of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased C by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased C by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.
CONCLUSION
Although C was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06083116.
Topics: Humans; Hydrochlorothiazide; Healthy Volunteers; Adult; Male; Drug Interactions; Young Adult; Female; Glucosides; Asian People; Dose-Response Relationship, Drug; Sodium-Glucose Transporter 2 Inhibitors; East Asian People
PubMed: 38828023
DOI: 10.2147/DDDT.S433377 -
Cureus Apr 2024The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as...
The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy. Febrile seizures are often a complication in a patient with DS and can lead to status epilepticus, necessitating measures to prevent triggers such as fever, electrolyte imbalance, or dehydration. An increased awareness and understanding of DS can facilitate the identification of warning signs. A two-year-old female with a past medical history of DS with focal and generalized features presented to the pediatric emergency department (ED) with a five-day history of cough, fever, and decreased oral intake. The patient's parents accompanied her and expressed concerns regarding the risk of seizures associated with a rise in body temperature, as they had been alternating between acetaminophen and ibuprofen to manage her fever with a maximum recorded temperature of 101.5℉. She exhibited signs of increased work of breathing, necessitating the administration of supplemental oxygen via nasal cannula. Blood samples were obtained and resulted in the development of metabolic acidosis. A respiratory panel confirmed the presence of an RSV infection, promoting the administration of breathing treatment with albuterol and ipratropium bromide. The patient was admitted for dehydration and was started on ½ normal saline/potassium chloride 20 mEq at 40 mL/hr. Additionally, her home medication regimen was resumed to minimize the risk of seizures. Given the patient's complications and increased risk of seizure, she was transferred to higher-level care where her status improved after the placement of a percutaneous endoscopic gastrostomy (PEG). This case underscores the complexities involved in managing patients with DS, particularly when complicated by respiratory illness and electrolyte imbalances that can lower the seizure threshold. This patient received a combination of diet and medications to prevent seizures, as well as allow for recovery and correction of the underlying metabolic acidosis. The transfer to a higher level of care in this case was necessary to allow for the specialized resources and expertise needed to handle this case.
PubMed: 38826591
DOI: 10.7759/cureus.59405 -
Scientific Reports Jun 2024Completion fluids play a vital role in well-related processes within the oil extraction industry. This article presents a comprehensive study of the properties and...
Completion fluids play a vital role in well-related processes within the oil extraction industry. This article presents a comprehensive study of the properties and performance of various brine solutions as completion fluids for different well and reservoir conditions. Attributes examined include density, corrosion resistance, temperature stability, compatibility with formation fluids, clay swelling potential and influence on wettability. The research highlights the significance of selecting appropriate completion fluids to optimize well and reservoir operations. Zinc chloride emerges as an excellent option for high density applications, while sodium chloride and potassium formate solutions are ideal for extreme cold conditions. Potassium acetate outperforms calcium chloride and potassium chloride and has excellent pH stability. The compatibility of completion fluids with formation water has been observed to be excellent, with no sedimentation or emulsion formation. Potassium acetate also experiences minimal clay swelling, making it suitable for clay-rich formations. On the other hand, calcium chloride has a higher clay swelling than most of the brines tested, making it less suitable for sandstone formations with a higher clay content than these brines. The research evaluates the water-wetting abilities of completion fluids in carbonate and sandstone formations. Potassium chloride and zinc chloride have the most significant impact in carbonate formations, while potassium acetate and potassium formate excel in sandstone formations. This study provides a comprehensive understanding of completion fluids, facilitating informed decisions that maximize operational efficiency, protect reservoir integrity, and enhance hydrocarbon recovery. The appropriate selection of completion fluids should align with specific well and reservoir conditions, considering the priorities of the application.
PubMed: 38824149
DOI: 10.1038/s41598-024-63303-5 -
Biopharmaceutics & Drug Disposition Jun 2024Bumetanide is used widely as a tool and off-label treatment to inhibit the Na-K-2Cl cotransporter NKCC1 in the brain and thereby to normalize intra-neuronal chloride...
Bumetanide is used widely as a tool and off-label treatment to inhibit the Na-K-2Cl cotransporter NKCC1 in the brain and thereby to normalize intra-neuronal chloride levels in several brain disorders. However, following systemic administration, bumetanide only poorly penetrates into the brain parenchyma and does not reach levels sufficient to inhibit NKCC1. The low brain penetration is a consequence of both the high ionization rate and plasma protein binding, which restrict brain entry by passive diffusion, and of brain efflux transport. In previous studies, bumetanide was determined in the whole brain or a few brain regions, such as the hippocampus. However, the blood-brain barrier and its efflux transporters are heterogeneous across brain regions, so it cannot be excluded that bumetanide reaches sufficiently high brain levels for NKCC1 inhibition in some discrete brain areas. Here, bumetanide was determined in 14 brain regions following i.v. administration of 10 mg/kg in rats. Because bumetanide is much more rapidly eliminated by rats than humans, its metabolism was reduced by pretreatment with piperonyl butoxide. Significant, up to 5-fold differences in regional bumetanide levels were determined with the highest levels in the midbrain and olfactory bulb and the lowest levels in the striatum and amygdala. Brain:plasma ratios ranged between 0.004 (amygdala) and 0.022 (olfactory bulb). Regional brain levels were significantly correlated with local cerebral blood flow. However, regional bumetanide levels were far below the IC (2.4 μM) determined previously for rat NKCC1. Thus, these data further substantiate that the reported effects of bumetanide in rodent models of brain disorders are not related to NKCC1 inhibition in the brain.
Topics: Animals; Bumetanide; Brain; Male; Rats; Sodium Potassium Chloride Symporter Inhibitors; Rats, Sprague-Dawley; Tissue Distribution; Solute Carrier Family 12, Member 2; Blood-Brain Barrier
PubMed: 38823029
DOI: 10.1002/bdd.2390 -
Current Problems in Cardiology Aug 2024Acute heart failure (AHF) is characterized by the emergence or intensification of symptoms and signs indicative of congestion or systemic hypoperfusion, stemming from an... (Review)
Review
Acute heart failure (AHF) is characterized by the emergence or intensification of symptoms and signs indicative of congestion or systemic hypoperfusion, stemming from an underlying structural or functional cardiac disorder. Intravenous loop diuretics play a pivotal role in achieving effective decongestion and ensuring clinical stability; the efficacy of these medications is crucial for determining the patient's hospital course and early outpatient progression. Individuals who exhibit a suboptimal response to diuretics or develop diuretic resistance (DR) are at an elevated risk for cardiovascular mortality and readmission due to AHF. However, there is a lack of standardized definition and diagnostic criteria for DR. Early identification of patients with DR is critical, as they may benefit from more aggressive decongestion strategies to mitigate this resistance. Natriuresis, the excretion of sodium in urine, serves as a direct measure of a diuretic's effectiveness. Low levels of natriuresis have been linked to poorer outcomes. Several studies have underscored the prognostic significance of natriuresis across various heart failure scenarios. However, the relationship between natriuresis and in-hospital DR has not been extensively studied. Observational research has indicated that inadequate natriuresis following the administration of loop diuretics correlates with a diminished diuretic response and an increased likelihood of mortality and heart failure rehospitalization. Further investigation is warranted to assess the predictive value of basal natriuresis concerning DR, in-hospital outcomes, and early outpatient cardiovascular events. This would help in identifying patients who are likely to respond poorly to diuretic therapy and may require alternative or more intensive treatment approaches.
Topics: Humans; Heart Failure; Natriuresis; Acute Disease; Drug Resistance; Diuretics; Prognosis; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 38821235
DOI: 10.1016/j.cpcardiol.2024.102688